Circulating androgen regulation by androgen-catabolizing gut bacteria in male mouse gut

Abstract

Abnormally high circulating androgen levels have been considered a causative factor for benign prostatic hypertrophy and prostate cancer in men. Recent animal studies on gut microbiome suggested that gut bacteria are involved in sex steroid metabolism; however, the underlying mechanisms and bacterial taxa remain elusive. Denitrifying betaproteobacteria Thauera spp. are metabolically versatile and often distributed in the animal gut. Thauera sp. strain GDN1 is an unusual betaproteobacterium capable of catabolizing androgen under both aerobic and anaerobic conditions. We administered C57BL/6 mice (aged 7 weeks) with strain GDN1 through oral gavage. The strain GDN1 administration caused a minor increase in the relative abundance of Thauera (≤0.1%); however, it has profound effects on the host physiology and gut bacterial community. The results of our ELISA assay and metabolite profile analysis indicated an approximately 50% reduction in serum androgen levels in the strain GDN1-administered male mice. Moreover, androgenic ring-cleaved metabolites were detected in the fecal extracts of the strain GDN1-administered mice. Furthermore, our RT – qPCR results revealed the expression of the androgen catabolism genes in the gut of the strain GDN1-administered mice. We found that the administered strain GDN1 regulated mouse serum androgen levels, possibly because it blocked androgen recycling through enterohepatic circulation. This study discovered that sex steroids serve as a carbon source of gut bacteria; moreover, host circulating androgen levels may be regulated by androgen-catabolizing gut bacteria. Our data thus indicate the possible applicability of androgen-catabolic gut bacteria as potent probiotics in alternative therapy of hyperandrogenism.

Prostate and gut: Any relationship? A narrative review on the available evidence and putative mechanisms

“…GM is involved into the process of deglucuronidation, thus being capable of increasing free androgen levels in the intestine. 59 Interestingly, some specific intestinal bacteria utilize sexual hormones, such as Steroidobacter Denitrificans, and Comamonas Testosteroni. 60 In fact, sex steroids serve as a carbon source for gut bacteria; eventually, host circulating androgen levels may be regulated by androgen-catabolizing gut bacteria.…”

“…60 In fact, sex steroids serve as a carbon source for gut bacteria; eventually, host circulating androgen levels may be regulated by androgen-catabolizing gut bacteria. 59 A group of researchers demonstrated that the levels of testosterone (T) correlated with bacterial density in the intestine. Using a specific, sensitive gas chromatography-tandem mass spectrometry method, they detected high levels of glucuronidated T and dihydrotestosterone (DHT) in small intestinal content of mice of both sexes, whereas in the distal intestine there were high levels of free DHT, exceeding serum levels by over 20-folds.…”

“…Hsiao et al found that the administered strain GDN1 regulated mouse serum androgen levels, by blocking androgen recycling mechanism via enterohepatic circulation. 59 In mice, an oral supplementation of Lactobacillus 63 Thus, androgen-catabolic gut bacteria may potentially represent a potent probiotic as an alternative or cotherapeutic agent for hyperandrogenism. 59…”

“…59 In mice, an oral supplementation of Lactobacillus 63 Thus, androgen-catabolic gut bacteria may potentially represent a potent probiotic as an alternative or cotherapeutic agent for hyperandrogenism. 59…”

“…Androgens are either reabsorbed prevalently in the small intestine or, when conjugated, are less susceptible to reabsorption and are excreted via feces. GM is involved into the process of deglucuronidation, thus being capable of increasing free androgen levels in the intestine 59 . Interestingly, some specific intestinal bacteria utilize sexual hormones, such as Steroidobacter Denitrificans , and Comamonas Testosteroni 60 .…”